with intravascular growth: report of two cases Ksenya V. Shelekhova & Dmitry V. Kazakov & Michal Michal Received: 19 April 2006 / Accepted: 13 October 2006 / Published online: 23 November 2006 # Springer-Verlag 2006 Abstract We present two cases of cotyledonoid dissecting leiomyoma of the uterus with intravascular involvement, which occurred in women aged 73 and 48 years. Grossly and microscopically, both neoplasms had an extrauterine cotyledonoid part and intrauterine dissecting fascicles of disorganized, swirled neoplastic smooth muscle with hydropic degeneration and foci of an intravascular growth (the latter was identified histologically). To our knowledge, the intravascular component of such a neoplasm is a very rare feature that has previously been described only in three cases in the literature. Keywords Leiomyoma of the uterus . Cotyledonoid . Intravascular . Dissecting . Intravenous leiomyomatosis Introduction Cotyledonoid dissecting leiomyoma (Sternberg tumor) is an unusual type of a benign uterine smooth muscle tumor that combines two main features: an exophytic component of smooth muscle grossly resembling placental tissue and an intrauterine component which irregularly extends into the myometrium between the fascicles of normal smooth muscle cells [1, 35, 7, 9]. This is a very rare variant of smooth muscle tumors with a distinctive gross appearance. Approximately 20 cases have been reported in the literature [35, 7, 9], and only three cases showed the association of a tumorous tissue with vessels [3]. We describe herein two additional cases of cotyle- donoid dissecting leiomyoma of the uterus with intravas- cular involvement, a very uncommon and infrequent feature to occur in this type of leiomyoma. Materials and methods Tissue samples were fixed in 4% formaldehyde and were paraffin-embedded. Sections (5 m thick) were stained with hematoxylin and eosin. A panel of immunohistochemical stains included anti- bodies against CD34 (QBEnd/10, 1:800, Neo Markers), CD31 (JC70A, 1:50, DakoCytomation), factor VIII-related antigen (F8/86, DakoCytomation), -smooth muscle actin (1A4; 1:1,000, DakoCytomation), muscle-specific actin (HHF35; 1:3,000, DakoCytomation), and desmin (D33, 1:3,000, DakoCytomation). For electron microscopic investigation, wet glutaralde- hyde-fixed tissue was available in one case. It was con- trasted in 1% osmium tetroxide and embedded into epoxy resin (Durcupan-Epon). Sections were cut 1 m thick, stained with toluidine blue, and examined by light micros- copy. Appropriate areas were selected, and thin sections were cut and stained with uranyl acetate and lead citrate and were examined with a Philips (Eindhoven, Holland) EM 208S electron microscope. Virchows Arch (2007) 450:119121 DOI 10.1007/s00428-006-0329-8 K. V. Shelekhova Department of Pathology, Petrovs Institute of Oncology, Saint-Petersburg, Russia D. V. Kazakov : M. Michal (*) Sikls Department of Pathology, Charles University, Medical Faculty Hospital, Alej Svobody 80, 30460 Pilsen, Czech Republic e-mail: michal@medima.cz Case reports Case 1 A 73-year-old woman underwent a laparotomy for a uterine mass. Her detailed gynecological history and follow-up were unavailable. Grossly, the tumor measured 8 cm and involved the uterus in the region of the fundus. There were numerous exophytic, rubbery reddish nodules that measured approximately 1.5 cm in diameter, resembled placental tissue, and extended into the broad ligament and projected into the pelvic cavity. Numerous ill-defined yellowish-white subserosal, intramyometrial, and submuco- sal nodules with a marked hydropic change represented the intrauterine component. Case 2 A 48-year-old woman, G3, P3 presented with a palpable abdominal mass, for which she underwent a total abdominal hysterectomy and salpingo-oophorectomy. Two years before presentation, the patient was diagnosed with myomatosis of the uterus, and 2 months before surgery, the patient started to experience pain, and the abdominal mass became palpable. She never used hormonal anticonceptives, but in the past, she had had an IUD for 21 years removed 2 years before the diagnosis of myomatosis. The patient was alive and well 2 years after surgery. Macroscopically, the enlarged uterus, measuring 13105 cm, revealed a bulbous tumorous mass measuring 945 cm, involving the fundus and the cornua, with extension into the broad ligament (Fig. 1). The cut surface of the uterus showed ill-defined intramural nodules of a tumor with variegated coloration. The adnexa were normal both grossly and microscopically. No intravascular growth was identified on gross exam- ination in either case. Microscopic and ultrastructural findings In both cases, there were variably sized micronodules of muscle fascicles, which were composed of disorganized Fig. 1 Case 2. Gross appearance of the uterus with the exophytic multinodular part of the tumor resembling placental tissue and extending into the broad ligament. The tumorous nodules were originally red in color and appear brown here because of long fixation in formalin Fig. 2 a Case 1. Intravascular extension of leiomyoma. b Case 2. Neoplastic leiomyomatous growth into the lumen of the small vein. c Case 2. CD31 staining: a tumorous mass in the lumen of the vein. d Case 2. Processes of the tumor dissect the myometrium. Note a nodule of swirled smooth muscle sur- rounded by a hydropic fibrous connective tissue 120 Virchows Arch (2007) 450:119121 hypertrophied smooth muscle cells and had a swirled appearance. The tumorous nodules were separated by a connective tissue with marked hydropic change and rich vascularity. Immunohistochemically, the tumor cells ex- hibited strong staining for desmin and smooth muscle actin. Within the leiomyomas, we discovered focal intra- vascular intrusion of the tumor masses. Foci of neoplastic leiomyomatous tissue sometimes entirely filled the lumens of the preexisting veins (Fig. 2a,b). CD31 and factor VIII-related antigen highlighted the endothelial cells of the blood vessels surrounding the foci of the intravascular growth of the leiomyoma (Fig. 2c). In other foci, dissecting tumor areas within the fascicles of normal-appearing myometrium were observed (Fig. 2d). There were neither nuclear atypia nor mitotic figures. No coagulative tumor- cell necrosis was observed. In both cases, mitotic figures were absent or rare (01 per 10 high-power fields). Case 2 was studied ultrastructurally [2]. The tumor was composed of cells that resembled normal smooth muscle cells and showed the characteristic folded nucleus. The cytoplasm contained intermediate filaments and microfila- ments with focal densities. There were also abundant collagen fibrils in the matrix. Discussion The classification of most benign smooth muscle tumors of the uterus is based on the combination of gross and microscopic features such as growth pattern, histologic appearance, association with vessels, and others [1, 37]. Therefore, numerous variants of uterine smooth muscle tumors may be manifestations of a common pathological process. Roth et al. [7], in 1996, noticed the associations and similarities between intravenous leiomyomatosis, infil- trating leiomyoma, multinodular hydropic leiomyoma, and cotyledonoid dissecting leiomyoma, and in view of these relationships, the authors believed that a cotyledonoid variant of intravenous leiomyomatosis can be anticipated. Indeed, Jordan et al. [3], in 2002, described three cases that demonstrated the features of intravenous leiomyomatosis. The authors regarded this type of leiomyoma as a novel entity and proposed the term cotyledonoid hydropic intravenous leiomyomatosis. However, only in one of the three cases reported by Jordan et al. was there an intimate association of the tumorous cells with vessels as detected macroscopically. Earlier, Norris and Pamley suggested that the term leiomyomatosis should be applied only to tumors in which intravascular extension could be detected on gross inspection, while lesions with intravascular growth seen only microscopically should be designated as leiomyoma. An extrauterine cotyledonoid part and intrauterine dissecting fascicles of disorganized, swirled neoplastic smooth muscle with hydropic degeneration and foci of intravascular growth of the tumor characterize both neo- plasms described in this report. These features are similar to those detected in previously described cases of Sternberg tumor [4, 5, 79]. In our cases, we did not find the intravascular growth macroscopically; hence, following the terminology suggested by Norris and Pamley, we designated both neoplasms reported herein as cotyledonoid dissecting leiomyoma of the uterus with intravascular growth and not as cotyledonoid hydropic intravenous leiomyomatosis. Foci of an intravascular growth may cause confusion and might imply a malignancy. The tumors however lack nuclear atypia, mitotic activity, or coagulative tumor ne- crosis, and, besides, well-differentiated smooth muscle cells and the abundance of collagen fibrils in the matrix infer the benign nature of the tumors. However, the small number of reported cases allows no conclusion on the biological course of the lesions. One of our patients was alive and well 2 years after surgery. In the series of Jordan, the follow-up (no evidence of disease at 5 years) was available only for one of the three patients. Further studies are needed to establish the exact biological nature of these tumors. References 1. Fukunaga M, Ushigome S (1998) Dissecting leiomyoma of the uterus with extrauterine extension. Histopathology 32:160164 2. Ghadially FN (1985) Diagnostic electron microscopy of the tumours, 2nd edn. Butterworths, London 3. Jordan LB, Al-Nafussi A, Beattie G (2002) Cotyledonoid hydropic intravenous leiomyomatosis: a new variant leiomyoma. Histopathology 40:245252 4. Kim MJ, Park YK, Cho JH (2002) Cotyledonoid dissecting leiomyoma of the uterus: a case report and review of the literature. J Korean Med Sci 17:840844 5. Menolascino-Brrata F, Garcia de Barriola V, Navajo de Gomez M, Garcia Tamayo J, Suarez JA, Hernandez Chacon AV (1999) Cotyledonoid dissecting leiomyoma (Sternberg tumor): an unusual form of leiomyoma. Pathol Res Pract 195:435438 6. Norris HJ, Parmley T (1975) Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis. A clinical and pathologic study of 14 cases. Cancer 36(6):21642178 7. Roth LM, Reed RJ, Sternberg WH (1996) Cotyledonoid dissecting leiomyoma of the uterus: the Sternberg tumor. Am J Surg Pathol 20 (2):14551461 8. Roth LM, Reed RJ (2000) Cotyledonoid leiomyoma of the uterus: report of a case. Int J Gynecol Pathol 19(3):272275 9. Saeed A-Sh, Hanaa B, Faisal AS, Najla A-M (2006) Cotyledonoid dissecting leiomyoma of the uterus: a case report of a benign uterine tumor with sarcomalike gross appearance and review of literature. Int J Gynecol Pathol 25:262267 Virchows Arch (2007) 450:119121 121